The Harvard Digestive Diseases Center (HDDC) represents a consortium of 60 investigators engaged in basic research relevant to digestive diseases. The scientific focus of the HDDC is epithelial structure and function. Four broad areas are represented: 1) epithelial cell function in digestion, absorption and malabsorption; 2) epithelial-microbial interactions in the pathogenesis of infectious diseases; 3) epithelial cell interactions involved in host defense and vaccine development, and 4) epithelial cell growth, differentiation and carcinogenesis. Members' laboratories are located primarily in Harvard Medical School and 3 affiliated hospitals: Children's Hospital Medical Center (CHMC), Beth Israel-Deaconess Medical Center (BIDMC), and Brigham and Women's Hospital (BMH); 7 neighboring institutions are also represented. The HDDC will begin its 15th year in September 1998 under the Directorship of Dr. Marian R. Neutra, Ph.D., with the Administrative Core (A) located in CHMC. In 1998, the research base for active members totals over $15,500,000 annually, and HDDC members are training 256 postdoctoral fellows and 37 predoctoral students. 26 Associate Members and HDDC (young investigators not yet independently funded) are also involved. Four newly revised Scientific Cores support the research of Center members and their trainees: an Imaging Core (B) for electron microscopy, light and epifluorescence microscopy, and confocal microscopy; an Epithelial Cell Function Core (C) for polarized epithelial cell-culture, electrophysiology and heterologous gene expression; a Biochemistry/Biophysics Core (D) for protein and lipid biochemistry, peptide libraries, and membrane fractionation and analysis; and an Immunology and Microbiology Core (E) for bacterial strains & culture, vectors, lymphocyte isolation, and analysis, and immunoassays. The HDDC funds Pilot-feasibility grants targeted to young investigators, and competitive Mini-sabbatical awards to foster new collaborations and the acquisition of new technologies. An Enrichment Program includes 4 seminar series focused on epithelial cell biology, mucosal immunology, microbiology, and adult and pediatric gastroenterology, and 2 annual half- day mini-symposia focused on recent advances in basic research relevant to digestive diseases. These HDDC programs work coordinately to address the long-term objective of the HDDC: to enhance our understanding and knowledge of digestive diseases, and thereby improve the care of patients with these conditions.